The accident happened at around 12.35pm on the A6106 at Hillcrest and involved a Vauxhall Astra and a Ford Kuga.
Emergency services attended the accident but the 41-year-old man driving the Astra was pronounced dead at the scene.
The woman driving the Ford, and her male passenger, were taken to Edinburgh Royal Infirmary with serious injuries.
The road was closed for five hours while an accident investigation was carried out.
Police Scotland is now appealing for information to establish exactly what happened to cause the accident and is asking anyone who saw anything to get in touch.
Sergeant Paul Ewing, Road Policing Division said: “Our thoughts are with the family and friends of the man who tragically lost his life and those who remain in hospital.
“Enquiries into the crash are ongoing and I am appealing to anyone who was driving on this stretch of road and who witnessed the crash to contact us.
“I would also be keen to hear from drivers who have dash-cam footage and would appeal to anyone who has not already spoken to officers to get in touch.”
If you have any information on the crash at Hillcrest, whether you witnessed it or were in the area at the time, you should contact Police Scotland on 101 quoting incident number 1196 of December 28, 2021.
Information can be submitted anonymously through Crimestoppers on 0800 555 111.